ASR490 (ASR 490) is a small molecule that binds to NRR of Notch1, specifically inhibits Notch1-mediated survival of colorectal cancer cells (IC50=0.6-1.2 uM); ASR490 overcomes Notch1 overexpression and inhibits the growth of HCT/Notch1 transfectants, reduces Notch1-mediated tumor burden in xenografts.

ASP9822 is a novel potent selective CDK7 inhibitor with IC50 of 4.3 nM, with anti-cancer activity.

ASP2205 (ASP2205 fumarate) is a potent, selective 5-HT2C receptor agonist with EC50 of 0.85/2.5 nM for human/rat 5-HT2C in the intracellular Ca2+ mobilization assays, respectively.ASP2205 showed partial agonistic action on human 5-HT2A receptor with EC50 of 96 nM, no agonistic action against 5-HT2B.ASP2205 (0.1-1 mg/kg, i.d.) significantly elevated the leak point pressure (LPP) in anesthetized rats in a dose-dependent manner.ASP2205 is a more potent and selective 5-HT2C receptor agonist than lorcaserin.

ASK120067 is a novel third-generation inhibitor of EGFR T790M (L858R/T790M IC50=0.3 nM, T790M IC50=0.5 nM), with selectivity over EGFR WT (IC50=6 nM).ASK120067 potently inhibited the EGFR L858R/T790M and EGFR T790M resistant mutants, with IC50 of 0.3 nM and 0.5 nM, respectively, as well as the EGFR exon19del sensitizing mutant (IC50= 0.5 nM).ASK120067 also displayed a favorable selectivity profile against a panel of 258 kinases.ASK120067 selectively inhibits the growth of EGFR-mutant cell lines and induces apoptosis, with IC50 values of 12 nM, 6 nM and 2 nM against NCI-H1975, PC-9, and HCC827 cells, respectively.ASK120067 dose-dependently inhibited EGF-induced EGFR L858R/T790M phosphorylation and consequent activation of the downstream molecules AKT and ERK in NCI-H1975 cells, with similar or even more effective potency than osimertinib.ASK120067 (5, 10 mg/kg once daily) demonstrated profound and selective antitumor efficacy in EGFR-mutant xenograft models in vivo.

ASIC1a inhibitor 5b is a highly selective and potent ASIC1a inhibitor, inhibits proton-evoked ASIC1a currents with an apparent IC50 of 27 nM at pH 6.7.ASIC1a inhibitor 5b can potently and selectively inhibit acid-induced activation of ASIC1a-containing channels, including both ASIC1a homotrimers and ASIC1a-ASIC2 heterotrimers, in a pH-dependent manner.ASIC1a inhibitor 5b binds to the acidic pocket of ASIC1a, exhibits a dramatic leftward shift under pH 6.7 activation of ASIC1a as compared to pH 6.0.ASIC1a inhibitor 5b protected neurons from ASIC1a-dependent cell death and is blood-brain barrier permeable.ASIC1a inhibitor 5b (5 mg/kg) attenuated neurological impairment and alleviated infarct volume in mouse MCAO model of ischemic stroke.

AS2690168 is a novel orally available, selective RANKL signal transduction inhibitor, reduces TRAP staining of sRANKL-stimulated RAW264 cells with IC50 of 0.28 uM, suppresses RANKL-induced osteoclastogenesis.AS2690168 suppressed soluble RANKL (sRANKL)-induced NFATc1 mRNA expression in RAW264 cells with 37.1% and 98.9% inhibiyion at 0.3 and 3.0 uM, respectively.AS2690168 also suppressed calcium release from parathyroid hormone-stimulated mouse calvaria with an IC50 value of 0.46 uM.AS2690168 (3 mg/kg, p.o.) completely suppressed the decrease in femoral bone mineral content in an sRANKL-induced osteopenic mice model, also significantly suppressed the decrease in femoral bone mineral density and increase in serum tartrate-resistant acid phosphatase-5b levels in ovariectomized rats at doses of 0.3, 1 and 3 mg/kg.AS260168 suppressed the increase in urine deoxypyridinoline in a rat prednisolone-induced osteoporosis model at 10 mg/kg.

AS2690168 is a novel orally available, selective RANKL signal transduction inhibitor, reduces TRAP staining of sRANKL-stimulated RAW264 cells with IC50 of 0.28 uM, suppresses RANKL-induced osteoclastogenesis.AS2690168 suppressed soluble RANKL (sRANKL)-induced NFATc1 mRNA expression in RAW264 cells with 37.1% and 98.9% inhibiyion at 0.3 and 3.0 uM, respectively.AS2690168 also suppressed calcium release from parathyroid hormone-stimulated mouse calvaria with an IC50 value of 0.46 uM.AS2690168 (3 mg/kg, p.o.) completely suppressed the decrease in femoral bone mineral content in an sRANKL-induced osteopenic mice model, also significantly suppressed the decrease in femoral bone mineral density and increase in serum tartrate-resistant acid phosphatase-5b levels in ovariectomized rats at doses of 0.3, 1 and 3 mg/kg.AS260168 suppressed the increase in urine deoxypyridinoline in a rat prednisolone-induced osteoporosis model at 10 mg/kg.

Artepillin C (CREB-CRTC2 inhibitor APC) is an inhibitor of CREB/CRTC2 interaction (IC50=24.5 uM), dissociates the CREB/CRTC2 complex, directly binds to CREB with Kd of 3.2 uM.CREB-CRTC2 inhibitor APC inhibits CRTC2 interacting with CREB-ZIP and reduces acetyltransferase activity of CBP by binding with CREB protein directly.Artepillin C attenuated gluconeogenesis in primary hepatocytes, reduced glucose output from primary hepatocytes induced by glucagon, remarkably decreased the mRNA accumulation of G6pc, Pck1, and Pgc-1α induced by glucagon in primary hepatocytes.|Artepillin C could ameliorate hyperlipidemia in obese mice.

ARN-75041 (ARN75041) is a potent, small molecule fusion inhibitor of arenavirus, inhibits pseudotyped entry of pGTOV and pCHAPV with EC50 of 1.7 and 15.3 nM, respectively. ARN-75041 demonstrated sub-nanomolar against native replicative LASV (LASV EC90<0.3 nM) and JUNV (EC90=6.2 nM).ARN-75041 also potently inhibits mutant T434I pTCRV variant with EC50 of 29 nM.ARN-75041 dramatically improved survival outcome and potently inhibited TCRV replication in serum and various tissues at doses of 10 and 35 mg/kg, provided highly significant post-exposure protection in mice against TCRV infection.

ARN-75039 (ARN75039) is a potent, small molecule fusion inhibitor of arenavirus, inhibits pseudotyped entry of pGTOV and pCHAPV with EC50 of 0.13 and 4.3 nM, respectively.ARN-75039 demonstrated sub-nanomolar EC50 activity against pTCRV that further translated to native wild-and NWAs, including LASV, JUNV and MACV, in pseudotyped virus assays and against native replicative LASV and JUNV.ARN-75039 also potently inhibits mutant T434I pTCRV variant with EC50 of 29 nM.ARN-75039 dramatically improved survival outcome and potently inhibited TCRV replication in serum and various tissues at doses of 10 and 35 mg/kg, provided highly significant post-exposure protection in mice against TCRV infection.

ARN24092 (ARN-4092) is a potent, selective inhibitor of Na+-K+-Cl- importer NKCC1, shows significant dose-dependent inhibition of NKCC1 in the Ca2+ influx assay (51.9% at 100 uM).ARN24092 did not show any significant inhibition of NKCC2 in the Cl-influx assay nor inhibition of KCC2 in the thallium (Tl) influx assay.ARN24092 (i.p, 0.6 mg/kg, daily) restored the short-term working memory of Ts65Dn mice in the T-maze test, completely restored associative memory in Ts65Dn mice in the contextual fear-conditioning (CFC) test, without side effects showed in health of the mice.

ARN23765 (ARN 23765) is a highly potent, pharmacological corrector of the mutant CFTR chloride channel with EC50 of 38 pM in cellular assays; ARN23765 is more than 5000-fold lower compared to presently available corrector drugs. ARN23765 also showed high efficacy, synergy with other types of correctors, and compatibility with chronic VX-770 potentiator.

AP-202 (AP202) is a highly potent and selective α4β2 nAChR antagonist with binding Ki of 18 nM, 57-fold selectivity over α3β4 receptor.AP-202 is agonist activity, also dispalys 40-fold, 10-fold and 90-fold selectivity over α4β4, α3β2, α3β4α5 receptors, does not activate α7 nAChR or block acetylcholine induced changes in membrane potential.AP-202 showed significant activity in blocking nicotine priming-induced as well as cue-induced reinstatement of nicotine seeking in vivo.

Antimicrobial peptide BING (IRIILRAQGALKI) is a thermostable 13-residue peptide that targets bacterial envelope stress response by suppressing cpxR expression in Gram-negative bacteria.BING downregulates efflux pump components and synergises the effect of antibiotics, and suppresses the development of antibiotic resistance.BING downregulated the expression of efflux pump components mexB, mexY and oprM in P. aeruginosa and significantly synergised the toxicity of antibiotics towards these bacteria.

anle145c is a small molecule inhibitor of amyloid aggregation and formation, inhibits human islet amyloid polypeptide (hIAPP)-induced death of INS-1E cells.anle145c has a special mode of action in which anle145c-stabilized oligomers act as a thermodynamic sink for the preferred aggregation state of hIAPP and anle145c.anle145c prevents hIAPP fibril formation in solution, and converts preformed hIAPP fibrils into non-toxic oligomers.anle145c is a promising candidate to inhibit protein aggregation in case of T2DM.

And1 inhibitor CH3 is potent acidic nucleoplasmic DNA-binding protein 1 (And-1) inhibitor, reducess And‐1 expression level in IGROV1 cells with IC50 of 2.08 uM.CH3 induces acidic nucleoplasmic DNA‐binding protein 1 (And‐1) degradation via the E3 ubiquitin ligase CUL4B‐mediated proteasome degradation pathway.CH3 promotes the interaction between And‐1 and CUL4B by altering And‐1 conformation.CH3 exhibits the significant inhibition in a broad range of cancer cells in vitro and in vivo.CH3 (20 mg/kg and 40 mg/kg) reduced tumor growth of ovarian IGROV1 and breast MCF7 xenografts at both treated doses.CH3 also could overcome cisplatin resistance in ovarian cancer.And1 is an important factor for deoxyribonucleic acid (DNA) replication and repair, is overexpressed in many types of cancer but not in normal tissues.

AN12855 (AN-12855) is potent, cofactor-independent M. tuberculosis InhA inhibitor, binds to and inhibits InhA with IC50 of 0.03 uM, shows potent activity against whole-cell M. tuberculosis H37Rv with IC90 of 0.09 uM; AN12855 demonstrates potent activity against drug-susceptible and drug-resistant strains of M. tuberculosis, exhibits comparable efficacy to the frontline antitubercular drug isoniazid (INH) in both acute and chronic models of TB infection with a lower potential for resistance development and shows in vitro activity against conventional KatG-mediated INH-resistant M. tuberculosis.

An anthelmintic effective agent for pinworms that shows to be a potent inhibitor of Wnt signaling with EC50 of 10 nM; binds to all CK1 family members in vitro at low nanomolar concentrations and selectively potentiates CK1α kinase activity; inhibits Wnt signaling downstream of β-catenin, and promotes Pygopus degradation; also is a potent inhibitor of HH signaling by reducing the stability of the Gli family of transcription factors.

AMY-101 (Cp40) is a peptidic inhibitor of the central complement component C3 for the management of patients with ARDS caused by SARS-CoV-2 infection.AMY-101 is a novel complement C3-targeted therapeutic based on the 3 rd-generation compstatin analog Cp40.

AMXI-5001 Hcl (AMXI 5001) is a novel, highly potent, orally active dual PARP1/2 (IC50 5/0.05 nM) and microtubule polymerization inhibitor, inhibits intracellular PAR formation with IC50 of 7 nM.AMXI-5001 binds to the catalytic domain of human PARP1 and is a weak tankyrase inhibitor (800-fold lower than IC50 towards either PARP1 or PARP2 enzymes).AMXI-5001 inhibited tubulin polymerization in a dose-dependent manner.AMXI-5001 exhibited selective antitumor cytotoxicity across a wide variety of human cancer cells with much lower IC50s than existing clinical PARP1/2 inhibitors.AMXI-5001 is highly active in both BRCA mutated and wild type cancers.AMXI-5001 elicited a remarkable In vivo preclinical anti-tumor activity in a BRCA mutated TNBC model induced complete regression of established tumors, including exceedingly large tumors, demonstrated superior anti-tumor effects compared to either single agent (PARP or microtubule) inhibitor or combination with both agents.

Amphihevir is a potent, selective HCV NS4B inhibitor with EC50 of 0.34 and 1.97 nM against the GT1a (H77) and GT1b replicon in luciferase assays.Amphihevir shows weaker acitivity against GT2a (JFH-1) (EC50=186 nM).Amphihevir shows EC50 3.13 nM and 18.16 nM with 100% human serum against GT1a and GT1b replicons using HCV-1b replicon cells test.Amphihevir reduced replicon RNA by nearly 6,300-fold (3.8 log10) at a concentration 25-fold greater than the EC90 (300 nM).Amphihevir was found to be inactive against other viruses, human kinases, and GPCRs, which implies its good selectivity.Amphihevir has good oral bioavailability and appropriate T1/2 in rats and dogs, showed good safety profiles in rats and dogs.Amphihevir is the first reported NS4B inhibitor that has advanced to clinical trials.

Aminoxyrone is a novel peptidometic C-terminal HSP90 inhibitor by targeting HSP90 dimerization via the C-terminal domain (CTD) with Kd of 27.4 uM; destabilizes BCR-ABL1 without inducing HSR in vitro and in vivo, additionally reduces pAKT-S473, pS6 expression and expression of client proteins associated with HSP90 chaperone activity, involving t-AKT, t-STAT5a, t-CRKL, cMYC, and BCL2; triggers the degradation of HSP90 client proteins without elevating the expression of HSPs (HSP70, HSP40 & HSP27); significantly inhibits cell growth and induces apoptosis of human leukemic stem cells (LSCs) with average EC50 of 20.94 uM, Aminoxyrone is effective in imatinib resistant CML and lacks heat shock response.

AMD3451 is a specific, dual CXCR5/CXCR4 antagonist with antiviral activity against a wide variety of HIV-1 and HIV-2 (IC50=1.2 to 26.5 uM) in vitro.AMD3451 has antiviral activity against a wide variety of R5, R5/X4, and X4 strains if HIV-1 and HIV-2 in various T-cell lines, CCR5- or CXCR4-transfected cells, PBMCs, and monocytes/macrophages.AMD3451 inhibited R5, R5/X4, and X4 HIV-1 primary clinical isolates in PBMCs (IC50, 1.8 to 7.3 uM), AMD3451 blocks R5 and X4 HIV-1 infection at the virus entry stage.AMD3451 dose-dependently inhibited the intracellular Ca2+ signaling induced by the CXCR4 ligand CXCL12 in T-lymphocytic cells and in CXCR4-transfected cells, as well as the Ca2+ flux induced by the CCR5 ligands CCL5, CCL3, and CCL4 in CCR5-transfected cells.AMD3451 did not interfere with chemokine-induced Ca2+ signaling through CCR1, CCR2, CCR3, CCR4, CCR6, CCR9, or CXCR3 and did not induce intracellular Ca2+ signaling by itself at 400 uM.AMD3451 inhibited CXCL12- and CCL3L1-induced endocytosis in CXCR4- and CCR5-transfected cells.AMD3451 does not inhibit the binding of CXCR4- or CCR5-specific MAbs.

AM9928 is a potent, covalent monoacylglycerol lipase (MAGL) inhibitor with IC50 of 8.9 nM (hMAGL).AM9928 covalently binds to and inactivates MAGL by carbamylation of the enzyme's catalytic Ser122 nucleophile.AM9928 inhibited adhesion and transmigration of breast cancer cells through human brain microvascular endothelial cells (HBMECs), inhibited TNBC's secretion of inflammatory cytokines such as IL-6 and IL-8, and the angiogenic factor VEGF-A.AM9928 inhibited in vivo changes in BBB permeability and decreased TNBC colonization in brain.MAGL inhibitor AM9928 is a novel treatment of TNBC tumor growth and TNBC-colonization in the brain.

AM6580 is a potent, covalent monoacylglycerol lipase (MAGL) inhibitor with IC50 of 3 nM (hMAGL).AM6580 covalently binds to and inactivates MAGL by carbamylation of the enzyme's catalytic Ser122 nucleophile.

AM237 is a selective TRPC5 channel activator that potently activated homomeric TRPC5:C5 channels (EC50=15–20 nM in Ca2+i assays).AM237 did not activate TRPC4:C4, TRPC4-C1, TRPC5-C1, TRPC1:C5, and TRPC1:C4 channels, or native TRPC1:C4 channels in A498 cells, but potently inhibited EA‐dependent activation of these channels with IC50 values ranging from 0.9 to 7 nM.AM237 (300 nM) did not activate or inhibit TRPC3, TRPC6, TRPV4, or TRPM2 channels.AM237 potentiated TRPC5:C5 channels activation by sphingosine‐1‐phosphate but suppressed activation evoked by (−)‐englerin A (EA).AM237 concentration‐dependently suppressed further activation of Ca2+ influx mediated by EA with IC50 of 13 nM, potentiated TRPC5:C5 activation by S1P.Pico145 is a competitive antagonist of AM237‐mediated TRPC5:C5 activation.

ALRN-6924 (ALRN6924) is a potent dual inhibitor of MDM2/MDMX.ALRN-6924 demonstrated potent anti-proliferative activity in a dose-dependent manner in two ER+ cell lines with WT TP53, MCF-7 and ZR-75-1, with IC50 values of 113 nM and 500 nM respectively.The combination of ALRN-6924 and chemotherapeutic agents synergistically inhibit cell proliferation in vitro, ALRN-6924 combined with paclitaxel reactivates p53 and induces cell cycle arrest and apoptosis in vitro.ALRN-6924 mutually enhances both paclitaxel and eribulin antitumor efficacy and inhibits tumor growth in vivo.

Alphastatin-C is a 14-amino acids peptide consisting of a C-terminal fragment of the α-chain of Fgn, is a potent inhibitor of bFGF induced endothelial cell (HUVEC-CS) activation in vitro.Alphastatin-C inhibits tumor angiogenesis and reduces melanoma tumor growth, inhibits the chorioallantoic membrane (CAM) angiogenesis in chick model.Alphastatin-C efficiently reduces tumor number and volume in a melanoma mice model, due to the impairment of tumor neovascularization in treated mice.Alphastatin-C is an efficient new antiangiogenic FGF-associated agent in vitro, and inhibitor of embryonic and tumor vascularization in vivo, also is an arteriogenic agent

ALKBH5 inhibitor 6 is a small molecule inhibitor of RNA 6-N-methyladenosine (m6A) demethylase ALKBH5, inhibits ALKBH5 RNA m6A demethylation activity with IC50 of 1.79 uM.

ALKBH5 inhibitor 3 is a small molecule inhibitor of RNA 6-N-methyladenosine (m6A) demethylase ALKBH5, inhibits ALKBH5 RNA m6A demethylation activity with IC50 of 0.84 uM.